The long term goal of the study is to understand, at the cellular level, the effects of mechanical and electrical stimuli on bone growth and remodeling. The objective of the next project period is to characterize the mechanical/electrical effects on the proliferation of bone and cartilage cells with respect to cellular specificity and stimulus transduction mechanism. The working hypothesis is that the effect of the physical stimuli (1) depends on the responsive cell (state of differentiation, cell cycle stage) and (2) is mediated by a membrane perturbation translated ino a cellular message (membrane depolarization, calcium, cyclic nucleotides). Mechanical and electrical perturbations of physiological magnitude will be applied, quantitatively, to: (1) long bones (organ explants), (2) proliferative and hypertrophying epiphyseal cartilage cells in primary and later cultures (3) calvaria cells, periosteal and endosteal, primary and later cultures (4) chondrosarcoma and its clones (5) osteosarcoma and its clones and to (6) synchronized populations of the above. The following parameters will be measured (1) to estimated proliferation: cell counts, 3H-thymidine incorporation into DNA, number of mitoses and fraction of labeled mitoses; (2) to investigate stimulus transduction: cyclic nucleotide levels, calcium, sodium an potassium tracer uptake and release from cells. The relationship between parameters (1) and (2) and the effects of experimental manipulations (drugs, etc.) on this relationship will be examined. The accumulated knowledge should contribute to the efficient utilization of mechanical and electrical stimuli in the treatment of hard tissue problems including: craniofacial anomalies, bone loss in periodontal disease, bone fractures and related disorders.